PhysiologyPhysiology
Skeletal Muscle Contraction
Connective TissueConnective TissueEndomysium
◦ Surrounds each muscle fiber (cell)◦ Attaches to Z-lines in each sarcomere
Perimysium◦ Surrounds bundles (fascicles) of muscle fibers◦ Attaches to endomysium
Epimysium◦ Attaches to the Perimysium◦ Continuous with tendon
SarcomereSarcomereRepeating Patterns within the
myofibrilsMyofibrils
◦Proteins within the myofibers◦Myosin◦Actin
Muscle AnatomyMuscle AnatomySarcolemma
◦Muscle fiber cell membraneMyofibrils
◦Highly organized bundles of contractile and elastic proteins
◦Carries out the work of contraction
Myofibrils = Contractile Organelles of Myofiber
Actin Myosin
Tropomyosin Troponin
Titin Nebulin
ContractileContractile
RegulatoryRegulatory
AccessoryAccessory
Contain 6 types of protein:
Titin and Nebulin
Titin: biggest protein known (25,000 aa); elastic! Stabilizes position of contractile filaments Return to relaxed location
Nebulin: inelastic giant protein Alignment of A & M
Changes in a Sarcomere during Contraction
MyosinMyosinMyo- muscleMotor protein of the myofibrilThick filamentAttaches to the M-line
◦Heads point towards Z-linesMyosin heads are clustered at
the ends of the filamentMyosin tails are bundled together
Role of calcium
Troponin complex
Tropomyosin
•Troponin and Tropomyosin bind to actinblock the actin – myosin binding sites
•Troponin is a calcium binding protein
ActinActinThin Filament
◦ Attached to Z-linesGlobular protein
◦ G-Actin◦ Has binding site for myosin head◦ Forms a Cross-Bridge when myosin binds to G-
actin◦ Five Actin proteins surround the myosin in 3-D
pattern
ActinActinTropomyosin
◦Protein that covers over the myosin binding site on G-Actin Myosin head can’t bind to G-Actin,
muscle relaxes
◦If the binding site on G-Actin is uncovered by removing Tropomyosin then myosin and actin bind, muscle contracts
ActinActinTroponin C
◦ Protein attached to Tropomyosin◦ When Troponin C changes shape it pulls on
Tropomyosin Calcium binding to Troponin C causes this
protein to change shape ◦ Tropomyosin moves and uncovers the binding
site on G-Actin, so Actin and Myosin can bind Contraction
Regulation of Contraction by Troponin and Tropomyosin
Tropomyosin blocks myosin binding site (weak binding possible but no powerstroke)
Troponin controls position of tropomyosin and has Ca2+ binding site
Ca2+ present: binding of A & M
Ca2+ absent: relaxation
Muscle AnatomyMuscle AnatomySarcoplasmic Reticulum
◦ Modified endoplasmic reticulum◦ Wraps around each myofibril like a piece of
lace◦ Stores Calcium
Terminal Cisternae◦ Longitudinal tubules
Transverse tubules (T-tubules)◦ Triad-two flanking terminal cisternae and one
t-tubule◦ T-tubules are continuous with cell membrane
When Troponin binds calcium it moves Tropomyosin away from the actin-myosin binding site
CaCa
Where does Calcium come from?
Intracellular storage called Sarcoplasmic Reticulum Surround each myofibril of the whole muscle Contains high concentration of calcium
Transverse Tubules connects plasma membrane to deep inside muscle
T-TubulesT-TubulesRapidly moves action potentials
that originate at the neuromuscular junction on the cell surface
Motor nerve
Neurotransmitter receptors
Membrane depolarization or APs carried deep into the muscle by T-tubules
+
T-tubule
SR
MyT-tubule
SR
SR
Ryanodine Receptor
Dihydropyridine receptor
myoplasm
T-tubule(extracellular)
SR
Myoplasm(intracellular)
++
++++
_ _ _ _ _ _
Ca++Ca++Ca++
_ _ _
+++
_ _ _+++
Ca++ pump
Myosin filament
Myosin head group
S2 link
Actin filament Binding sites
Stretching of the link generates tension
Weakbinding
Strongbinding
Equal and opposite forceon thick filament
Why do thin filaments move?
Net forceNet force
Sliding Filament TheorySliding Filament TheoryWhen myosin binds to the
binding site on G-actin muscular contraction occurs.
The more myosin that bind to G-actin the greater the force of contraction
Calcium must be present
Sliding Filament TheorySliding Filament Theory Cross Bridge
◦ Myosin in the High Energy Configuration binds to G-Actin
◦ ADP + Pi are bonded to the myosin head when the cross bridge forms
Power Stroke◦ When the myosin and actin bind the myosin head
changes shape◦ Myosin pulls the actin and pulls on the Z-line◦ Sarcomere shortens◦ ADP+Pi no longer binds to myosin head
Sliding Filament TheorySliding Filament TheoryATP binds to the myosin head
◦Myosin changes to its Low Energy Confirmation
◦In the Low Energy Confirmation Myosin breaks its bonds with Actin Rigor Mortis
Lack of ATP Build up of Lactic Acid
Sliding Filament TheorySliding Filament TheoryATPase
◦ATP is hydrolyzed to ADP + Pi◦ATPase is on the myosin head◦Myosin changes shape back to its
High Energy Confirmation
Sliding Filament TheorySliding Filament TheorySome Myosin heads detach from
Actin while other heads continue to keep their attachments◦No slipping of the Z-lines◦Contraction is held in place
Rigor mortis
Actin + myosin Actomyosin complex
What if we don’t have this?
XATP
Events at Neuromuscular Events at Neuromuscular JunctionJunctionConverts a chemical signal from
a somatic motor neuron into an electrical signal in the muscle fiber
Events at Neuromuscular Events at Neuromuscular JunctionJunctionAcetylcholine (Ach) is released from the
somatic motor neuronAch initiates an action potential in the
muscle fiberThe muscle action potential triggers
calcium release from the sarcoplasmic reticulum
Calcium combines with troponin C and initiates contractions
Events at Neuromuscular Events at Neuromuscular JunctionJunctionAch binds to cholinergic
receptors on the motor end plateNa+ channels open
◦Na+ influx exceeds K+ efflux across the membrane
End-Plate Potential (EPP)◦EPP reaches threshold and initiates a
muscle action potential
Events at Neuromuscular Events at Neuromuscular JunctionJunctionAction Potentials move down the
membrane◦K+ builds up in the t-tubules◦Depolarization occurs
Calcium gates on the SR opens Calcium diffuses into the cytoplasm of
the cell
Excitation-Contraction CouplingExcitation-Contraction Coupling
The process where muscle action potentials initiate calcium signals that in turn activates a contraction-relaxation cycle
Initiation of Contraction
Excitation-Contraction Coupling explains how you get from AP in axon to contraction in sarcomere
ACh released from somatic motor neuron at the Motor End Plate
AP in sarcolemma and T-Tubules
Ca2+ release from sarcoplasmic reticulum
Ca2+ binds to troponin
Nicotinic cholinergic receptors on motor end plate = Na+ /K+ channels
Net Na+ entry creates EPSP
AP to T-tubules
DHP (dihydropyridine) receptors in T-tubules sense depolarization
Details of E/C Coupling
Nicotinic Cholinergic Receptors
DHP (dihydropyridine) receptors open Ca2+ channels in t-tubules
Intracytosolic [Ca2+]
Contraction
Ca2+ re-uptake into SR
Relaxation
Excitation-Contraction CouplingExcitation-Contraction Coupling
High cytosolic Calcium levels binds to Troponin C◦ Tropomyosin moves to the “on” position and
contraction occursCalcium-ATPase pumps Calcium back
into the SR The more myosin heads that binds to
actin to stronger the force of contraction
1. Synaptic Depolarization of the plasma membrane is carried into the muscle by T-Tubules
2. Conformational change of dihydropyridine receptor directly opens the ryanodine receptor calcium channel
3. Calcium flows into myoplasm where it binds troponin
4. Calcium pumped back into SR
Summary of events
Neuromuscular JunctionNeuromuscular JunctionThe more terminal boutons to
attach to myofibers the greater the control of the muscle.
Recruitment◦The greater the number of terminal
boutons attached to myofibers there is more fine control of the muscle
Excitation-Contraction CouplingExcitation-Contraction Coupling
Twitch◦A single contraction-relaxation cycle
in a skeletal muscle fiber◦A single action potential in a muscle
fiberLatent Period
◦Between the muscle action potential ◦Time required for excitation-
contraction coupling to take place
Is There Truth In Advertising?Is There Truth In Advertising?
Is the banana company telling the truth when they claim that bananas being high in Potassium actually prevents or relieves muscle cramps?
If so, how does this increase in Potassium relieve muscle cramps?
If not, why not and how do we actually relieve muscle cramps?
Muscle Contraction and ATP Muscle Contraction and ATP SupplySupplyPhosphocreatine
◦Backup energy source◦Quick energy used up in approx. 15
minutes
Causes of FatigueCauses of FatigueCentral Fatigue
◦Subjective feelings of tiredness◦Arises in the CNS◦Psychological fatigue precedes
physiological fatigue in the muscles Subjective feelings of tiredness Low pH may cause fatigue
Muscle Fiber Classification
Oxidative only
Oxidative or glycolytic
Muscle Adaptation to Exercise
Endurance training: More & bigger
mitochondria
More enzymes for aerobic respiration
More myoglobin
no hypertrophy
Resistance training: More actin & myosin
proteins & more sarcomeres
More myofibrils
muscle hypertrophy
Causes of FatigueCauses of FatiguePeripheral Fatigue
◦Arises between the neuromuscular junction and the contractile elements of the muscle
◦Ach depletion, neuromuscular junction receptor loss Myasthenia Gravis
Skeletal Muscle TypesSkeletal Muscle TypesFast-twitch muscle fibers (type II)
◦White Fibers Low Myoglobin
◦Develops tension two to three times faster than slow-twitch fibers
◦Splits ATP more rapidly to complete contraction faster
◦Fatigues quickly
Skeletal Muscle TypesSkeletal Muscle TypesSlow-twitch Muscle Fibers (Type I)◦Red◦High Myoglobin levels◦Slow to Fatigue
ContractionsContractionsIsometric Contractions
◦Creates force without movementIsotonic Contractions
◦Moves loads
During skeletal muscle contraction the During skeletal muscle contraction the binding of the myosin head to G-actin binding of the myosin head to G-actin occurs at which step?occurs at which step?
A. Cross bridgeB. Power strokeC. Working strokeD. Force stroke
During the cross bridge the myosin During the cross bridge the myosin head is in the ____ configuration.head is in the ____ configuration.
A. Low energyB. High energyC. Medium energyD. Power energy
Name the connective tissue Name the connective tissue layer that surrounds a fascicle layer that surrounds a fascicle in skeletal muscle.in skeletal muscle.A. EndomysiumB. EpimysiumC. PerimyseumD. TendonE. Epicardium
Name the functional unit of Name the functional unit of skeletal muscle.skeletal muscle.A. SarcolemmaB. Saroplasmic ReticulumC. SarcomereD. Myosin
The thick filament is also The thick filament is also referred to asreferred to asA. ActinB. MyosinC. TropomyosinD. Troponin CE. G Actin
Which protein in G-Actin is Which protein in G-Actin is responsible for blocking the bind responsible for blocking the bind site of myosin?site of myosin?A. TropomyosinB. Troponin CC. Sarcoplasmic ReticulumD. Sarcolemma
During skeletal muscle During skeletal muscle contraction Calcium is stored contraction Calcium is stored in thein theA. SarcolemmaB. SarcomereC. Sarcoplasmic ReticulumD. Golgi ApparatusE. Transverse Tubules
The build-up of potassium in the The build-up of potassium in the _______ causes the resting _______ causes the resting membrane potential of skeletal membrane potential of skeletal muscle to depolarize.muscle to depolarize.
A. SarcolemmaB. Sarcoplasmic reticulumC. Transverse tubuleD. Tropomyosin
Which enzyme is located on Which enzyme is located on the myosin head?the myosin head?
A. ATP synthaseB. ATP aseC. ATP reductaseD. PhophodiesteraseE. Oxidase
During cross bridge During cross bridge formation myosin will bind to formation myosin will bind to ________.________.
A. Troponin CB. TropomyosinC. G-ActinD. Myosin
The phenomenon of rigor The phenomenon of rigor mortis is a direct result ofmortis is a direct result of
A. The breaking of myosin bonds by ATP
B. The breaking of actin bonds by ATPC. The inability of the myosin cross
bridges to combine with single amino acids
D. The loss of ATP in dead muscle cells